DESCRIPTION: (Applicant's Description) Colorectal cancer is the second leading cause of cancer deaths in the United States. Dietary studies have frequently found an inverse association of this cancer with the intake of fruits and vegetables. Laboratory assays are now available that provide us with the opportunity to identify specific components of the diet that may be protective against this common disease. In addition, biomarkers are available to clarify the association of obesity and physical inactivity with colorectal cancer. For these reasons, we propose to do a prospective study, which will collect blood and urine samples from about 39,000 male and female Oahu residents of Caucasian, Japanese or Native Hawaiian ancestry, who participated in the Multi-ethnic Cohort Study from 1993 to 1996. They completed a 26-page mailed questionnaire, which included information on demographics, diet, anthropometry, physical activity, sunlight exposure, alcohol intake, and medical history. After an average 3 years of follow-up, about 262 incident cases will be identified among the 39,000 participants by the Hawaii Tumor Registry. Each case will be matched to two controls on sex, race, age at phlebotomy, month of blood collection, fasting status, and survival status in a nested case-control study design. The study will determine if there are inverse associations of colorectal cancer with plasma and red blood cell folate (reflecting intake of leafy green vegetables, oranges, etc.), total urinary isothiocyanates (reflecting intake of cruciferous vegetables), serum 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D, as well as positive associations with insulin resistance (based on serum glucose and insulin values) and plasma insulin-like growth factors (specifically insulin-like growth factor I and II, and insulin-like growth factor binding protein 3). The modifying effects of methylenetetrahydrofolate reductase gene polymorphism on folate metabolism and of glutathione-S-transferase gene polymorphism on isothiocyanate metabolism will also be studied.